Abstract

The conformational properties of the protected seven-residue C-terminal fragment of the lipo-peptaibol antibiotic Trichogin A IV (Boc-Gly-Gly-Leu-Aib-Gly-Ile-Leu-OMe) has been examined in CDC13 and (CD3),S0 by 'H-nmr. Evidence for a multiple beta-turn conformation [type I' at Gly(l)-Gly(2), type II at Leu(3)-Aib(4). and a type I' at Aib(4)-Gly(S)] suggests that Leu (3) has preferred an extended or semiextended conformation over a helical conformation in CDCl3. This structure is thus in contrast to earlier observations of seven-residue peptides containing a single central Aib preferring helical conformations in both solution and crystalline states. A structural transition to a frayed right-handed helix is observed in (CD3)2SO. These results suggest that nonhelical conformations may be important in Gly-rich peptides containing Aib. Further, the presence of amino acids with contradictory influences on backbone conformational freedom can lead to well-defined conformational transitions even in small peptides.